Here's a depressing abstract:
Contraindicated Use of Cisapride
Impact of Food and Drug Administration Regulatory Action
Walter Smalley, MD, MPH; Deborah Shatin, PhD; Diane K. Wysowski, PhD; Jerry Gurwitz, MD; Susan E. Andrade, DSc; Michael Goodman, PhD; K. Arnold Chan, MD, DSc; Richard Platt, MD, MS; Stephanie D. Schech, MPH; Wayne A. Ray, PhD
Context Cisapride, a gastrointestinal tract promotility agent, can cause life-threatening cardiac arrhythmias in patients susceptible either because of concurrent use of medications that interfere with cisapride metabolism or prolong the QT interval or because of the presence of other diseases that predispose to such arrhythmias. In June 1998, the US Food and Drug Administration (FDA) determined that use of cisapride was contraindicated in such patients and informed practitioners through additions to the boxed warning in the label and a "Dear Health Care Professional" letter sent by the drug's manufacturer.
Objective To evaluate the impact of the FDA's 1998 regulatory action regarding contraindicated use of cisapride.
Design and Setting Analysis of data for the 1-year periods before (July 1997-June 1998) and after (July 1998-June 1999) the regulatory action from the population-based, pharmacoepidemiology research databases of 2 managed care organizations (sites A and B) and a state Medicaid program (site C).
Participants Patients with at least 180 days of prior enrollment in 1 of the 3 sites who were prescribed cisapride at least once in the period before (n = 24 840) or after (n = 22 459) regulatory action. Patients could be included in both cohorts.
Main Outcome Measures Proportion of cisapride users in each period for whom cisapride use was contraindicated by the product label, based on computerized patient medical encounter records.
Results In the year prior to regulatory action, cisapride use was contraindicated for 26%, 30%, and 60% of users in study sites A, B, and C, respectively. In the year after regulatory action, use was contraindicated for 24%, 28%, and 58% of users, a reduction in contraindicated use of approximately 2 per 100 cisapride users at each site. When the analysis was restricted to new users of cisapride after regulatory action, only minor reductions in contraindicated use were found.
Conclusion The FDA's 1998 regulatory action regarding cisapride use had no material effect on contraindicated cisapride use. More effective ways to communicate new information about drug safety are needed.
JAMA. 2000;284:3036-3039
(See also the News thread for an NPR report on this).
Bottom line of course is that the FDA will be less willing to approve drugs that have serious side effects for some identifiable subset of patients. Maybe calls into question some of the pharmacogenomics proposals unless some system is put into place to ensure compliance. (CELG's thalidomide program is an example of such a system).
Peter |
